Our objective is to investigate the role of the brain in the mechanism of initiation of cardiac arrhythmias, particularly ventricular fibrillation (VF). We have shown that cardiac responses and arrhythmias can be influenced by several experimentally defined states of the central nervous system including: 1. psychological stress evoked by unfamiliar surroundings, 2. slow wave and rapid eye movement sleep stages, 3. tone-shock cardiac conditioning, 4. electric brain stimulation, and 5. functional brain blockade in a particular cerebral system. Our electrophysiological studies have suggested a specific brain system, involving the frontal lobe, mediates the effects of psychological stress on the myocardium. Local cryogenic blockade in this system prevents the initiation of VF in the ischemic heart. The implication of this result is, if pharmacologic intervention could be achieved to duplicate the effect of the cryogenic blockade, then the lethal consequences of myocardial ischemia could be prevented. Currently we are using two new methods that we developed to study the neural tissue in the conscious brain as it responds to psychologically or physically stressful stimuli: 1. rapid freeze-fixation by a cryoplate to investigate neurochemical responses and 2. long-term intracellular recording by a floating micropipette to study membrane biophysical responses as well as synaptic pharmacology.